Because sprouting of intact systems may underlie recovery after central nervous system damage, it is important to define the conditions which are most favorable to the formation of persistent sprouts. Similarity of transmitter systems in a given population of destroyed axons and of spared axons may determine which system will successfully reinnervate a denervated area. One aim of the proposed investigation is to compare the response of systems which share the same transmitter as a population of destroyed dorsal root afferent fibers (Transmitter-Like Paradigm) and those which do not (Transmitter-Unlike Paradigm). Applying correlative morphological and quantitative biochemical methods to examples of the Transmitter-Like Paradigm, we will determine: 1) the amount of fall and recovery after rhizotomy of substance P (SP), which is found in both dorsal roots and interneurons; and 2) loss and recovery of glutamate (GLU) after dorsal rhizotomy, using high-affinity uptake of 3H-GLU. As a necessary preliminary to the GLU-study we will determine the normal distribution of the high-affinity GLU uptake system and its sources of origin. As examples of the Transmitter-Unlike Paradigm we will determine whether amounts of Met-Enkephalin and/or GABA (found in interneurons but not in dorsal roots) increase after rhizotomy. The outcome of this correlative morphological and quantitative biochemical investigation will indicate whether transmitter specificity is one factor which influences the outcome of sprouting. In the same model we will examine directly if competition is an important determinant of sprouting when several pathways overlap in a partially denervated region. Finally, we intend to distinguish between two possible stimuli for sprouting: loss of synaptic input andloss of transmitter.